gamma-Crystallins are associated with cataract in both human and animal models. They may also have stress related roles in other eye tissues, notably retina. We have shown that they can play a role in stabilization of cytoskeleton in lens. g-Crystallins have highly unusual solution properties that fit them for high protein concentration environments. They have stable, tightly folded structures but can unfold to form amyloid like fibrils. We have studied unfolding/refolding in members of the gS-crystallin family from birds and mammals. A single amino acid residue which differs between birds and mammals appears to have a key role in determining long term stability of the protein fold and the ability of the protein to adopt an alternative conformation which seems to resist formation of light scattering aggregates. We have crystallized and solved the three-dimensional structure of chicken gS-crystallin, the first gS to be crystallized. We have found that crystallization is dependent on the unusual L16 residue specific to birds. this residue also affects other important aspects of intermolecular interactions.the crystal structure reveals an unexpected mode for gS dimerization. In addition we have crystallized a variant of mouse gS, revealing a remarkable structure that appears to be an aggregation intermediate. This adds important insight into the processes that lead to cataract. We have also begun collaborative studies of crystallin aggregates using atomic force microscopy